We have continued our studies of volume regulation in the giant red cells of Amphiuma in preparation for their use in micropuncture measurements. Amphiuma red cells regulate their volume in anisotonic media by utilizing transport mechanism(s) that selectively control the cells' ability to gain or lose electrolytes. The process whereby cells enlarge in hypertonic media involves an amiloride sensitive Na uptake. This finding has led the suggestion that the Na transporter in Amphiuma erythrocytes and that present at the mucosal border of "tight" epithelia is similar. Additional evidence is support of this hypothesis has been presented.